The pathogenesis of recurrent ocular chlamydial infections is thought to be immunologically mediated (i.e., hypersensitivity). However, due to the lack of an appropriate animal model of ocular chlamydial infections, the immunological response to chlamydial antigens during infection and challenge has not been characterized. We have chosen to study the immunopathology of guinea pig inclusion conjunctivitis (GPIC), a Chlamydia psittaci strain which produced both ocular and genital infections in guinea pigs. We have clinically, microbiologically, and histologically characterized both primary GPIC and a delayed hypersensitivity response induced during primary GPIC. The delayed hypersensitivity response is to a heat-labile, genus-specific chlamydial antigen. This ocular response can be induced during chlamydial infections at mucosal sites other than the conjunctiva including genital and intestinal mucosa. The immunodominant antigens during primary infection and following challenge have been identified and recombinant clones expressing these antigens have been isolated. Several purified membrane components from GPIC elementary bodies (EBs) and a clone expressing the genus-specific epitope of lipopolysaccharide have been tested as potential protective antigens. None of these preparations tested have produced protective immunity.